In the pharmaceutical industry, there are different types of environments classified as grade A, B, C, D, etc., grade A traditionally corresponding to the cleanest environmental classification grade. The cleaner the grade is, the stricter the standards are that govern tolerance with respect to the presence of contaminants, such as microorganisms, residues of biological/biotechnological materials (proteins, etc.), fine particles and dust. Traditionally, clean rooms in a GMP (Good Manufacturing Process) environment are aseptic rooms that have zones A, B, C and D through which the different substances designed to become pharmaceutical products pass.
In this context, grade A corresponds to the final environment in which the injectable pharmaceutical products are distributed into final containers, typically tubes, blisters or vials after passing through filling needles. These tubes, blisters or vials are of course sterilized beforehand and treated so as to minimize their particulate content. They are also inert with respect to the pharmaceutical product that they contain inasmuch as they release very few or no particles or chemical compounds into the solution. In general, these containers must meet very strict standards to guarantee patient safety.
Consequently, during the production method, the medium containing the substance intended to become a pharmaceutical product undergoes different steps such as purifications, filtrations or other transformations, which means that the substance goes from a zone with a particular grade toward a zone with a higher grade or from one container to another, etc. These containers or zones have an outside environment and an inside environment, the outside environment essentially being less clean or less likely to be clean than the inside environment. Thus, a pouch containing a substance intended to be distributed in grade A cannot itself be in grade A if it has previously been exposed to an environment with a lower grade, since the outside of the pouch may be contaminated and therefore contaminate the inside environment of the grade A zone, and consequently, the pharmaceutical product itself.
Conversely, some pharmaceutical products that are particularly active, such as antineoplastic products, for example, or certain products resulting from biotechnology using the live viral vectors, require confining the distribution operations in a closed enclosure in order to minimize the risk of contamination of the surrounding space, i.e., the medium outside the compartment.
Today, various solutions for transfers between zones of different grades or different contamination levels have been developed, which all aim to reduce the risk of contamination of a zone by the environment of another zone. As an example, for the aseptic filling of tubes/vials/blisters with pharmaceutical products, there are grade A “glove boxes” that contain the tubes/vials/blisters as well as filling needles and that comprise a communication orifice through which the content of a reservoir situated in an outside environment (potentially of a less clean grade) is transferred. These communication orifices are equipped with devices making it possible to minimize the risk of contamination by using connecting members that cooperate tightly with the communication orifice, without risking placing the pharmaceutical product to be transferred in contact with surfaces that could have been contaminated by exposure to an environment with a lower grade.
A connecting member as mentioned in the beginning of this document is known from document EP 1,312,096. More particularly, this connecting member is described as ensuring the aseptic transfer of a fluid starting from a container situated in an environment with a given grade toward smaller containers present in an environment with a higher grade, the content of the containers having to be completely sterile.
Such transfers are critical in particular in the pharmaceutical industries, where it is imperative for the packaging of large volumes of stock solutions in smaller volumes to be done without risking contaminating the solution to be distributed. To that end, the smaller containers are filled in a compartment aseptically isolated from the outside environment, the fluid being pumped for example from a pouch, passing through the tubing of the connecting member, then being distributed in the smaller containers, which are filled using an aseptic filling device.
During these operations, the connecting member, connected at one of its ends to the container of the stock solution and at its other end (situated inside the sterile compartment) to an aseptic fluid filling device, plays a key role inasmuch as it constitutes the interface allowing the aseptic transfer of the fluid between the outside surrounding medium (typically less clean, but not necessarily) and the inside environment of the compartment. To ensure complete isolation between the inside environment of the compartment and the outside environment of the compartment, connecting means respectively present at the communication orifice of the compartment and at the connecting member are provided so as to form a tight connection preventing any entry of contaminants in the compartment. This tight connection is ensured by a placement in contact, via the aforementioned connecting members, of the rigid wall of the compartment with the connecting member, which is also rigid, a flexible sealing gasket being able to be present between these two rigid members in order to reinforce the tight nature of the connection.
Furthermore, in prior art document EP 1,312,096, a cartridge surrounds and removably cooperates with the part of the connecting member that enters the compartment. More particularly, the cartridge protects the connecting part that enters the compartment, and which itself is clean and sterile. A removable closing device inside the compartment is also provided that cooperates with said cartridge. The cartridge and the removable closing device are arranged relative to one another such that no contaminant can compromise the stability of the compartment where the filling of the small containers takes place. In fact, the removable closing device confines of the contaminants that may be present on the cartridge between its inner wall and the outer wall of the cartridge. When the movable closing device is removed, it is provided to drive the simultaneous withdrawal of the cartridge without any contaminant being able to reach the inside environment of the compartment inasmuch as the contaminants are confined between the outer wall of the cartridge and the inner wall of the removable closing device.
Unfortunately, even if the fluid transfers between environments with different classifications are indeed done in a sterile manner with such a device known from the state of the art, the fact nevertheless remains that the fluid must necessarily pass through the tubing of the connecting member. Yet the connecting member, and therefore the tubing of the latter, traditionally being manufactured from a plastic material (for example, polybutylene terephthalate, or PBT), contamination of the fluid crossing through it may be observed following the contact of the fluid with said plastic material. This contamination of the passing fluid can, for example, take the form of a release of particles or chemical compounds from this plastic material, or on the contrary, the form of an adsorption, on the walls of the tubing, of the chemical or biological components knowingly contained in the fluid. As minimal as they may be, these contaminations by the material of the tubing cannot be tolerated regarding sensible injectable pharmaceutical products such as certain vaccines, for example. Consequently, the use of such connecting members requires validating the absence of risk of contamination by interaction between the material of the connecting member and the transferred product, such validations generally being lengthy, restrictive and costly. To date, such connecting members are therefore limited to certain fluids and applications. Furthermore, another drawback lies in the fact that the current connecting members have a tubing whereof the diameter is invariable and subject to manufacturing methods in particular based on the use of molds. Yet, for example, depending on the viscosity of the fluid to be transferred or the low quantity of product available, this fixed diameter of the connecting member is not optimal in all scenarios.
FR1499227 proposes to use a funnel set for a tube-tube connection. This solution presents different drawbacks. There is an empty space between the two tubes when they are put in communication. This is a source of contamination: in particular, small-size contaminants, from air for instance, can fill this empty space. Furthermore, the flexible element for joining the two tubes is a point of weakness. Connection between the two tubes is thus not very secured, and one could have liquid passing from one tube to another that comes into contact with possible contaminated elements such as internal walls of the main passage or communication orifice of the wall separating the clean environment from the dirty one.